Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

HIV infection and anaemia do not affect HbA1c for the detection of diabetes in black South Africans: Evidence from the Durban Diabetes Study.

OBJECTIVE: South Africa has a high burden of HIV infection and anaemia. These conditions may cause HbA1c to over- or underestimate glycaemia; however, this has not been comprehensively investigated in African populations. We assessed the association of anaemia, HIV infection and antiretroviral therapy (ART) with HbA1c , and implications for the detection and diagnosis of diabetes, in a black South African population. RESEARCH DESIGN AND METHODS: In this population-based cross-sectional study in eThekwini municipality (Durban), South Africa, we assessed HbA1c and conducted oral glucose tolerance tests (OGTTs), HIV diagnostic tests and full blood count measurements among 1067 participants without a history of diabetes diagnosis. Linear regression was used to examine differences in HbA1c by anaemia (comparator: no anaemia), or HIV and ART (comparator: no HIV) status. HbA1c -based diabetes prevalence was compared with OGTT-based prevalence among individuals with anaemia and with untreated and ART-treated HIV. RESULTS: In adjusted analyses, normocytic and microcytic anaemia were associated with higher HbA1c compared with no anaemia, whereas macrocytic anaemia and ART-treated HIV were associated with lower HbA1c compared with no anaemia and no HIV, respectively. However, magnitudes of association were small (range: ß  = -3.4 mmol/mol or -0.31%, p < 0.001 [macrocytic anaemia] to ß = 2.1 mmol/mol or 0.19%, p < 0.001 [microcytic anaemia]). There was no significant difference in diabetes prevalence based on HbA1c or OGTT among individuals with anaemia (2.9% vs. 3.3%, p = 0.69), untreated HIV (1.6% vs. 1.6% p = 1.00) or ART-treated HIV (2.9% vs. 1.2%, p = 0.08). CONCLUSIONS: Our results suggest that anaemia and HIV status appear unlikely to materially affect the utility of HbA1c for diabetes detection and diagnosis in this population. Further studies are needed to examine these associations in sub-Saharan African populations.

The African Genome Variation Project shapes medical genetics in Africa.

Given the importance of Africa to studies of human origins and disease susceptibility, detailed characterization of African genetic diversity is needed. The African Genome Variation Project provides a resource with which to design, implement and interpret genomic studies in sub-Saharan Africa and worldwide. The African Genome Variation Project represents dense genotypes from 1,481 individuals and whole-genome sequences from 320 individuals across sub-Saharan Africa. Using this resource, we find novel evidence of complex, regionally distinct hunter-gatherer and Eurasian admixture across sub-Saharan Africa. We identify new loci under selection, including loci related to malaria susceptibility and hypertension. We show that modern imputation panels (sets of reference genotypes from which unobserved or missing genotypes in study sets can be inferred) can identify association signals at highly differentiated loci across populations in sub-Saharan Africa. Using whole-genome sequencing, we demonstrate further improvements in imputation accuracy, strengthening the case for large-scale sequencing efforts of diverse African haplotypes. Finally, we present an efficient genotype array design capturing common genetic variation in Africa.

Highly Diverse Hepatitis C Strains Detected in Sub-Saharan Africa Have Unknown Susceptibility to Direct-Acting Antiviral Treatments.

The global plan to eradicate hepatitis C virus (HCV) led by the World Health Organization outlines the use of highly effective direct-acting antiviral drugs (DAAs) to achieve elimination by 2030. Identifying individuals with active disease and investigation of the breadth of diversity of the virus in sub-Saharan Africa (SSA) is essential as genotypes in this region (where very few clinical trials have been carried out) are distinct from those found in other parts of the world. We undertook a population-based, nested case-control study in Uganda and obtained additional samples from the Democratic Republic of Congo (DRC) to estimate the prevalence of HCV, assess strategies for disease detection using serological and molecular techniques, and characterize genetic diversity of the virus. Using next-generation and Sanger sequencing, we aimed to identify strains circulating in East and Central Africa. A total of 7,751 Ugandan patients were initially screened for HCV, and 20 PCR-positive samples were obtained for sequencing. Serological assays were found to vary significantly in specificity for HCV. HCV strains detected in Uganda included genotype (g) 4k, g4p, g4q, and g4s and a newly identified unassigned g7 HCV strain. Two additional unassigned g7 strains were identified in patients originating from DRC (one partial and one full open reading frame sequence). These g4 and g7 strains contain nonstructural (ns) protein 3 and 5A polymorphisms associated with resistance to DAAs in other genotypes. Clinical studies are therefore indicated to investigate treatment response in infected patients. Conclusion: Although HCV prevalence and genotypes have been well characterized in patients in well-resourced countries, clinical trials are urgently required in SSA, where highly diverse g4 and g7 strains circulate.

Sociodemographic inequities associated with participation in leisure-time physical activity in sub-Saharan Africa: an individual participant data meta-analysis.

BACKGROUND: Leisure-time physical activity (LTPA) is an important contributor to total physical activity and the focus of many interventions promoting activity in high-income populations. Little is known about LTPA in sub-Saharan Africa (SSA), and with expected declines in physical activity due to rapid urbanisation and lifestyle changes we aimed to assess the sociodemographic differences in the prevalence of LTPA in the adult populations of this region to identify potential barriers for equitable participation. METHODS: A two-step individual participant data meta-analysis was conducted using data collected in SSA through 10 population health surveys that included the Global Physical Activity Questionnaire. For each sociodemographic characteristic, the pooled adjusted prevalence and risk ratios (RRs) for participation in LTPA were calculated using the random effects method. Between-study heterogeneity was explored through meta-regression analyses and tests for interaction. RESULTS: Across the 10 populations (N = 26,022), 18.9% (95%CI: 14.3, 24.1; I2 = 99.0%) of adults (≥ 18 years) participated in LTPA. Men were more likely to participate in LTPA compared with women (RR for women: 0.43; 95%CI: 0.32, 0.60; P < 0.001; I2 = 97.5%), while age was inversely associated with participation. Higher levels of education were associated with increased LTPA participation (RR: 1.30; 95%CI: 1.09, 1.55; P = 0.004; I2 = 98.1%), with those living in rural areas or self-employed less likely to participate in LTPA. These associations remained after adjusting for time spent physically active at work or through active travel. CONCLUSIONS: In these populations, participation in LTPA was low, and strongly associated with sex, age, education, self-employment and urban residence. Identifying the potential barriers that reduce participation in these groups is necessary to enable equitable access to the health and social benefits associated with LTPA.

Genome-wide association study of type 2 diabetes in Africa.

AIMS/HYPOTHESIS: Genome-wide association studies (GWAS) for type 2 diabetes have uncovered >400 risk loci, primarily in populations of European and Asian ancestry. Here, we aimed to discover additional type 2 diabetes risk loci (including African-specific variants) and fine-map association signals by performing genetic analysis in African populations. METHODS: We conducted two type 2 diabetes genome-wide association studies in 4347 Africans from South Africa, Nigeria, Ghana and Kenya and meta-analysed both studies together. Likely causal variants were identified using fine-mapping approaches. RESULTS: The most significantly associated variants mapped to the widely replicated type 2 diabetes risk locus near TCF7L2 (p = 5.3 × 10-13). Fine-mapping of the TCF7L2 locus suggested one type 2 diabetes association signal shared between Europeans and Africans (indexed by rs7903146) and a distinct African-specific signal (indexed by rs17746147). We also detected one novel signal, rs73284431, near AGMO (p = 5.2 × 10-9, minor allele frequency [MAF] = 0.095; monomorphic in most non-African populations), distinct from previously reported signals in the region. In analyses focused on 100 published type 2 diabetes risk loci, we identified 21 with shared causal variants in African and non-African populations. CONCLUSIONS/INTERPRETATION: These results demonstrate the value of performing GWAS in Africans, provide a resource to larger consortia for further discovery and fine-mapping and indicate that additional large-scale efforts in Africa are warranted to gain further insight in to the genetic architecture of type 2 diabetes.

Sociodemographic patterns of health insurance coverage in Namibia.

INTRODUCTION: Health insurance has been found to increase healthcare utilisation and reduce catastrophic health expenditures in a number of countries; however, coverage is often unequally distributed among populations. The sociodemographic patterns of health insurance in Namibia are not fully understood. We aimed to assess the prevalence of health insurance, the relation between health insurance and health service utilisation and to explore the sociodemographic factors associated with health insurance in Namibia. Such findings may help to inform health policy to improve financial access to healthcare in the country. METHODS: Using data on 14,443 individuals, aged 15 to 64 years, from the 2013 Namibia Demographic and Health Survey, the association between health insurance and health service utilisation was investigated using multivariable mixed effects Poisson regression analyses, adjusted for sociodemographic covariates and regional, enumeration area and household clustering. Multivariable mixed effects Poisson regression analyses were also conducted to explore the association between key sociodemographic factors and health insurance, adjusted for covariates and clustering. Effect modification by sex, education level and wealth quintile was also explored. RESULTS: Just 17.5% of this population were insured (men: 20.2%; women: 16.2%). In fully-adjusted analyses, education was significantly positively associated with health insurance, independent of other sociodemographic factors (higher education RR: 3.98; 95% CI: 3.11-5.10; p < 0.001). Female sex (RR: 0.83; 95% CI: 0.74-0.94; p = 0.003) and wealth (highest wealth quintile RR: 13.47; 95% CI: 9.06-20.04; p < 0.001) were also independently associated with insurance. There was a complex interaction between sex, education and wealth in the context of health insurance. With increasing education level, women were more likely to be insured (p for interaction < 0.001), and education had a greater impact on the likelihood of health insurance in lower wealth quintiles. CONCLUSIONS: In this population, health insurance was associated with health service utilisation but insurance coverage was low, and was independently associated with sex, education and wealth. Education may play a key role in health insurance coverage, especially for women and the less wealthy. These findings may help to inform the targeting of strategies to improve financial protection from healthcare-associated costs in Namibia.

A cross-sectional analysis of ITN and IRS coverage in Namibia in 2013.

BACKGROUND: Achieving vector control targets is a key step towards malaria elimination. Because of variations in reporting of progress towards vector control targets in 2013, the coverage of these vector control interventions in Namibia was assessed. METHODS: Data on 9846 households, representing 41,314 people, collected in the 2013 nationally-representative Namibia Demographic and Health Survey were used to explore the coverage of two vector control methods: indoor residual spraying (IRS) and insecticide-treated nets (ITNs). Regional data on Plasmodium falciparum parasite rate in those aged 2-10 years (PfPR2-10), obtained from the Malaria Atlas Project, were used to provide information on malaria transmission intensity. Poisson regression analyses were carried out exploring the relationship between household interventions and PfPR2-10, with fully adjusted models adjusting for wealth and residence type and accounting for regional and enumeration area clustering. Additionally, the coverage as a function of government intervention zones was explored and models were compared using log-likelihood ratio tests. RESULTS: Intervention coverage was greatest in the highest transmission areas (PfPR2-10 ≥ 5%), but was still below target levels of 95% coverage in these regions, with 27.6% of households covered by IRS, 32.3% with an ITN and 49.0% with at least one intervention (ITN and/or IRS). In fully adjusted models, PfPR2-10 ≥ 5% was strongly associated with IRS (RR 14.54; 95% CI 5.56-38.02; p < 0.001), ITN ownership (RR 5.70; 95% CI 2.84-11.45; p < 0.001) and ITN and/or IRS coverage (RR 5.32; 95% CI 3.09-9.16; p < 0.001). CONCLUSIONS: The prevalence of IRS and ITN interventions in 2013 did not reflect the Namibian government intervention targets. As such, there is a need to include quantitative monitoring of such interventions to reliably inform intervention strategies for malaria elimination in Namibia.

Evaluating the Impact of Functional Genetic Variation on HIV-1 Control.

Background: Previous genetic association studies of human immunodeficiency virus-1 (HIV-1) progression have focused on common human genetic variation ascertained through genome-wide genotyping. Methods: We sought to systematically assess the full spectrum of functional variation in protein coding gene regions on HIV-1 progression through exome sequencing of 1327 individuals. Genetic variants were tested individually and in aggregate across genes and gene sets for an influence on HIV-1 viral load. Results: Multiple single variants within the major histocompatibility complex (MHC) region were observed to be strongly associated with HIV-1 outcome, consistent with the known impact of classical HLA alleles. However, no single variant or gene located outside of the MHC region was significantly associated with HIV progression. Set-based association testing focusing on genes identified as being essential for HIV replication in genome-wide small interfering RNA (siRNA) and clustered regularly interspaced short palindromic repeats (CRISPR) studies did not reveal any novel associations. Conclusions: These results suggest that exonic variants with large effect sizes are unlikely to have a major contribution to host control of HIV infection.

The Use of Different International References to Assess Child Anthropometric Status in a Malaysian Population.

OBJECTIVE: To assess the prevalence of child underweight, overweight, and obesity in a Malaysian population according to 3 international references because classification of anthropometric status may differ according to the reference used to express body mass index (BMI). STUDY DESIGN: We assessed data from 6414 children aged 6-18 years, collected by the South East Asia Community Observatory. Child underweight, overweight, and obesity were expressed according to 3 internationally used BMI references: World Health Organization 2007, International Obesity Task Force 2012, and Centers for Disease Control and Prevention 2000. We assessed agreement in classification of anthropometric status among the references using Cohen's kappa statistic and estimated underweight, overweight, and obesity prevalence according to each reference using mixed effects Poisson regression. RESULTS: There was poor to moderate agreement between references when classifying underweight, but generally good agreement when classifying overweight and obesity. Underweight, overweight, and obesity prevalence estimates generated using the 3 references were notably inconsistent. Overweight and obesity prevalence estimates were higher using the World Health Organization reference vs the other 2, and underweight prevalence was up to 8.5% higher and obesity prevalence was about 4% lower when using the International Obesity Task Force reference. CONCLUSIONS: The choice of reference to express BMI may influence conclusions about child anthropometric status and malnutrition prevalence. This has implications regarding strategies for clinical management and public health interventions.

Urbanicity and lifestyle risk factors for cardiometabolic diseases in rural Uganda: a cross-sectional study.

BACKGROUND: Urban living is associated with unhealthy lifestyles that can increase the risk of cardiometabolic diseases. In sub-Saharan Africa (SSA), where the majority of people live in rural areas, it is still unclear if there is a corresponding increase in unhealthy lifestyles as rural areas adopt urban characteristics. This study examines the distribution of urban characteristics across rural communities in Uganda and their associations with lifestyle risk factors for chronic diseases. METHODS AND FINDINGS: Using data collected in 2011, we examined cross-sectional associations between urbanicity and lifestyle risk factors in rural communities in Uganda, with 7,340 participants aged 13 y and above across 25 villages. Urbanicity was defined according to a multi-component scale, and Poisson regression models were used to examine associations between urbanicity and lifestyle risk factors by quartile of urbanicity. Despite all of the villages not having paved roads and running water, there was marked variation in levels of urbanicity across the villages, largely attributable to differences in economic activity, civil infrastructure, and availability of educational and healthcare services. In regression models, after adjustment for clustering and potential confounders including socioeconomic status, increasing urbanicity was associated with an increase in lifestyle risk factors such as physical inactivity (risk ratio [RR]: 1.19; 95% CI: 1.14, 1.24), low fruit and vegetable consumption (RR: 1.17; 95% CI: 1.10, 1.23), and high body mass index (RR: 1.48; 95% CI: 1.24, 1.77). CONCLUSIONS: This study indicates that even across rural communities in SSA, increasing urbanicity is associated with a higher prevalence of lifestyle risk factors for cardiometabolic diseases. This finding highlights the need to consider the health impact of urbanization in rural areas across SSA. Please see later in the article for the Editors' Summary.

Genetic variants influencing circulating lipid levels and risk of coronary artery disease.

OBJECTIVE: Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. METHODS AND RESULTS: We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)). CONCLUSIONS: We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.

Distinct genetic architectures and environmental factors associate with host response to the γ2-herpesvirus infections.

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr Virus (EBV) establish life-long infections and are associated with malignancies. Striking geographic variation in incidence and the fact that virus alone is insufficient to cause disease, suggests other co-factors are involved. Here we present epidemiological analysis and genome-wide association study (GWAS) in 4365 individuals from an African population cohort, to assess the influence of host genetic and non-genetic factors on virus antibody responses. EBV/KSHV co-infection (OR = 5.71(1.58-7.12)), HIV positivity (OR = 2.22(1.32-3.73)) and living in a more rural area (OR = 1.38(1.01-1.89)) are strongly associated with immunogenicity. GWAS reveals associations with KSHV antibody response in the HLA-B/C region (p = 6.64 × 10-09). For EBV, associations are identified for VCA (rs71542439, p = 1.15 × 10-12). Human leucocyte antigen (HLA) and trans-ancestry fine-mapping substantiate that distinct variants in HLA-DQA1 (p = 5.24 × 10-44) are driving associations for EBNA-1 in Africa. This study highlights complex interactions between KSHV and EBV, in addition to distinct genetic architectures resulting in important differences in pathogenesis and transmission.

Characterisation and correlates of stunting among Malaysian children and adolescents aged 6-19 years.

Background: Despite emerging evidence regarding the reversibility of stunting at older ages, most stunting research continues to focus on children below 5 years of age. We aimed to assess stunting prevalence and examine the sociodemographic distribution of stunting risk among older children and adolescents in a Malaysian population. Methods: We used cross-sectional data on 6759 children and adolescents aged 6-19 years living in Segamat, Malaysia. We compared prevalence estimates for stunting defined using the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) references, using Cohen's κ coefficient. Associations between sociodemographic indices and stunting risk were examined using mixed-effects Poisson regression with robust standard errors. Results: The classification of children and adolescents as stunted or normal height differed considerably between the two references (CDC v. WHO; κ for agreement: 0.73), but prevalence of stunting was high regardless of reference (crude prevalence: CDC 29.2%; WHO: 19.1%). Stunting risk was approximately 19% higher among underweight v. normal weight children and adolescents (p = 0.030) and 21% lower among overweight children and adolescents (p = 0.001), and decreased strongly with improved household drinking water sources [risk ratio (RR) for water piped into house: 0.35, 95% confidence interval (95% CI) 0.30-0.41, p < 0.001). Protective effects were also observed for improved sanitation facilities (RR for flush toilet: 0.41, 95% CI 0.19-0.88, p = 0.023). Associations were not materially affected in multiple sensitivity analyses. Conclusions: Our findings justify a framework for strategies addressing stunting across childhood, and highlight the need for consensus on a single definition of stunting in older children and adolescents to streamline monitoring efforts.

Energy intake at breakfast and weight change: prospective study of 6,764 middle-aged men and women.

To investigate the association between percentage of total daily energy intake consumed at breakfast and weight change in middle-aged men and women, the authors analyzed data from a prospective population-based cohort study from Norfolk, United Kingdom. Participants were 6,764 men and women aged 40-75 years at baseline (1993-1997). Participants completed a 7-day food diary at baseline, and objective measurements of height and weight were carried out at baseline and follow-up (1998-2000). Mean baseline body mass index (weight (kg)/height (m)(2)) was lowest among persons in the highest quintile of percentage of daily energy consumed at breakfast (mean values were 26.0 in the highest quintile and 26.3 in the lowest quintile), despite higher daily total energy intake in this group. Although all participants gained weight, increased percentage of daily energy consumed at breakfast was associated with relatively lower weight gain (adjusted beta coefficient = -0.021, 95% confidence interval: -0.035, -0.007; p = 0.004). The association between percentage of daily energy intake consumed at breakfast and weight gain was independent of age, sex, smoking, total energy intake, macronutrient intake, social class, and physical activity. Redistribution of daily energy intake, so that more energy is consumed at breakfast and less energy is consumed later in the day, may help to reduce weight gain in middle-aged adults.

Socioeconomic position and risk of short-term weight gain: prospective study of 14,619 middle-aged men and women.

BACKGROUND: The association between socioeconomic position in middle age and risk of subsequent, short-term weight gain is unknown. We therefore assessed this association in a prospective population based cohort study in Norfolk, UK. METHODS: We analysed data on 14,619 middle-aged men and women (aged between 40-75 at baseline) with repeated objective measures of weight and height at baseline (1993-1997) and follow up (1998-2000). RESULTS: During follow up 5,064 people gained more than 2.5 kg. Compared with the highest social class, individuals in the lowest social class had around a 30% greater risk of gaining more than 2.5 kg (OR 1.29; 95% CI 1.11-1.51; p for trend = 0.002). This association remained statistically significant following adjustment for sex, age, baseline BMI, smoking, and follow up time (OR 1.25; CI 1.07-1.46; p for trend <0.001). We also found no material difference between unadjusted models and those including all confounders and potential mediators. CONCLUSION: Individuals of low socioeconomic position are at greatest risk of gaining weight during middle age, which is not explained by classical correlates of socioeconomic position and risk factors for obesity.

Association between early life antibiotic use and childhood overweight and obesity: a narrative review.

BACKGROUND: Recent research implicates antibiotic use as a potential contributor to child obesity risk. In this narrative review, we examine current observational evidence on the relation between antibiotic use in early childhood and subsequent measures of child body mass. METHODS: We searched PubMed, Web of Science and the Cochrane Library to identify studies that assessed antibiotic exposure before 3 years of age and subsequent measures of body mass or risk of overweight or obesity in childhood. RESULTS: We identified 13 studies published before October 2017, based on a total of 6 81 332 individuals, which examined the relation between early life antibiotic exposure and measures of child body mass. Most studies did not appropriately account for confounding by indication for antibiotic use. Overall, we found no consistent and conclusive evidence of associations between early life antibiotic use and later child body mass [minimum overall adjusted odds ratio (aOR) reported: 1.01, 95% confidence interval (95% CI) 0.98-1.04, N = 2 60 556; maximum overall aOR reported: 2.56, 95% CI 1.36-4.79, N = 616], with no clinically meaningful increases in weight reported (maximum increase: 1.50 kg at 15 years of age). Notable methodological differences between studies, including variable measures of association and inclusion of confounders, limited more comprehensive interpretations. CONCLUSIONS: Evidence to date is insufficient to indicate that antibiotic use is an important risk factor for child obesity, or leads to clinically important differences in weight. Further comparable studies using routine clinical data may help clarify this association.

HIV treatment is associated with a two-fold higher probability of raised triglycerides: Pooled Analyses in 21 023 individuals in sub-Saharan Africa.

BACKGROUND: Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. METHODS: Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models. FINDINGS: Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I2=45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies. INTERPRETATION: Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.

Anthropometric and cardiometabolic risk factors in parents and child obesity in Segamat, Malaysia.

Background: There is little evidence regarding risk factors for child obesity in Asian populations, including the role of parental anthropometric and cardiometabolic risk factors. We examined the relation between parental risk factors and child obesity in a Malaysian population. Methods: We used data from health and demographic surveillance conducted by the South East Asia Community Observatory in Segamat, Malaysia. Analyses included 9207 individuals (4806 children, 2570 mothers and 1831 fathers). Child obesity was defined based on the World Health Organization 2007 reference. We assessed the relation between parental anthropometric (overweight, obesity and central obesity) and cardiometabolic (systolic hypertension, diastolic hypertension and hyperglycaemia) risk factors and child obesity, using mixed effects Poisson regression models with robust standard errors. Results: We found a high burden of overweight and obesity among children in this population (30% overweight or obese). Children of one or more obese parents had a 2-fold greater risk of being obese compared with children of non-obese parents. Sequential adjustment for parental and child characteristics did not materially affect estimates (fully adjusted relative risk for obesity in both parents: 2.39, 95% confidence interval: 1.82, 3.10, P < 0.001; P for trend < 0.001). These associations were not modified by parental or child sex. We found no consistent evidence for associations between parental cardiometabolic risk factors and child obesity. Conclusions: Parental obesity was strongly associated with child obesity in this population. Further exploration of the behavioural and environmental drivers of these associations may help inform strategies addressing child obesity in Asia.

Correction: Prevalence of Dyslipidaemia and Associated Risk Factors in a Rural Population in South-Western Uganda: A Community Based Survey.

[This corrects the article DOI: 10.1371/journal.pone.0126166.].